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Doppler ultrasonography in evaluation of PDA shunting
852
Editorial correspondence
The Journal of Pediatrics May 198I
T a b l e . T h e clinical a n d l a b o r a t o r y d a t a
Patient 1 Cytochemical staining PAS Sudan Black Esterase Specific Nonspecific Immunologic marker Pre- and postblood transfusion Hemoglobin (gm/dl) White blood cell (per mm:') Blast (%) Platelet (per m m ~) Uric acid (mg/dl) Calcium (mg/dl) Phosphorus (mg/dl) Urea nitrogen (mg/dl) Creatinine (mg/dl) Quantity of blood exchanged Outcome
Patient 2
Patient 3
Negative Negative
Positive Negative
Positive Negative
Negative Negative T-cell (with anterior mediastinal mass) Pre Post
Negative Negative Non-B, N o n T-cell
Negative Negative Non-B, N o n T-cell
]
Post
11.9
2.5
8.8
5.1 1.0 million
331,000
130,000
128,000
39,300
4,400
6,500
93 38,000 11.3 9.3 3.4
45,000 7.0 8.0 4.2
85 20,000 10.5 9.5 5.5
82 166,000 8.8
0. 250,000 5.8 9.4 4.3
0. 90,000 ----
18
16
12
--
--
Partial (89 of blood volume) Relapsed in marrow 5 m o and died 8 mo after diagnosis
Not done
Negative Negative Not applicable
Pre
4.7
1. l
Negative Positive
Post
12.0
1.0
16.0 -
Partial (89 of blood volume) C C R 10 m o currently
-
Partial (~A of blood volume) C C R - 1 3 m o currently
Patient 5
Positive Negative
Pre
8.6
1.2
Patient 4
Pre
Post
Pre
Post
14.3
3.3
9.6
500*
240,000
133,000
23,000 8.5 8.7 1.8
96 13,000 4.9 9.8 3.9
50,000 3.2 8.4 4.6
86 85,000 11.4 10.3 5.4
I4
21.
18
0.8
0.8
Partial (zA of blood volume) C C R - 4 yr currently (one year off theraPY)
1.5
0.9
Partial (~A of blood volume) Failed to attain remission, died 7 m o after diagnosis
CCR = Continuous complete remission. *Following two exchange transfusions with concomitant cyclophosphamide, solucortef and vincristine.
anemia with partial exchange transfusion, A m J Dis Child 131"60 1977. Simone JV, Verzosa MD, and Rudy JA: Initial features and prognosis in 363 children with acute lymphocytic leukemia, Cancer 36"2099, 1975.
Doppler ultrasonography in evaluation of PDA shunting To the Editor: The report by Serwer and colleagues' describing the use of continuous wave Doppler ultrasonography to assess descending aorta flow reversal during diastole in premature infants with patent ductus arteriosus (PDA) is of great interest. As an alternative to descending aorta signals, we have recorded signals from the brachial (BA) and femoral (FA) arteries of 74 premature infants suspected of having a PDA. The directional flow patterns observed in RBA and FA recordings have been usefuI in detecting "silent" PDA, and approximating diastolic run-off.
A "pencil" probe and directional Doppler unit (Parks electronics Model 806-C, Beaverton, Ore.) were used. The bidirectional audiosignal was monitored stereophonically and recorded at 50 ram/second on a Beckman polygraph. With large, surgically proven PDA (n = 6) FA reverse/ forward ratio ( R / F ) averaged 0.33 preoperatively, and was always < 0.05 postoperatively; RBA R / F was 0.26 preoperatively and < 0.05 postoperatively. With moderate left-to-right P D A shunting (n = 31), where subsequent events provided compelling evidence that a PDA had been present (e.g., m u r m u r disappearance, surgical, or autopsy visualization), a typical pattern was seen: R / F 0.20 to 0.33 in FA, while R / F in RBA was < 0.05; R / F in left BA was more variable. This pattern (FA reverse flow > RBA reverse flow) appears to be specific for ductus shunting and is consistent with the cineaortographic and pressure wave dynamics described by Spach et al.'-' Provided the limbs are warm, and no catheter or thrombus obstructs the artery, false positives (for reverse flow) are not seen. False negatives can occur if the vascular resistance of the limbs is lowered with respect to other organs, e.g., following skeletal muscle paralysis. A false negative also occurred in one infant in
Volume 98 Number 5
Editorial correspondence
whom a catheter-obstructed RFA showed no flow reversal while flow reversal was seen in the unobstructed LFA. Doppler evaluation of arterial flow patterns in the presence of a PDA is a valuable noninvasive tool, and we congratulate the Duke University group on a thoughtful and important report. Martin H. Lees, M.D. James D. Newcomb, B.A. Cecille O. Sunderland, M.D. Paul Droukas, M.D. John W. Reynolds, M.D. Department of Pediatrics University of Oregon Health Sciences Center Portland, OR 97201
assess the presence or absence of PDA shunting, as Lees and coworkers have shown. Gerald A. Serwer, M.D. Brenda E. Armstrong, M.D. Page A. W. Anderson, M.D. Department of Pediatrics Division of Pediatric Cardiology Duke University Medical Center Durham, NC 27710 REFERENCES
1.
2. REFERENCES
1.
2.
Serwer GA, Armstrong BE, and Anderson PAW! N o n invasive detection of retrograde descending aortic flow in infants using continuous wave Doppler ultrasonography. J PEDIATR 97:394, 1980. Spach MS, Serwer GA, Anderson PAW, Canent RV Jr, and Levin AR: Pulsatile aortopulmonary pressure-flow dynamics of patent ductus arteriosus in patients with varying hemodynamic states, Circulation 61:110, 1980.
Reply To the Editor: The excellent work of Lees and coworkers again confirms the utility of using continuous wave Doppler ultrasonography to detect abnormal arterial flow patterns in the presence of certain disease states, in this case, the presence of a patent ductus arteriosus. Detection of flow in the femoral and brachial arteries is easily performed and, unlike our studies, does not require a flat probe but can utilize a more standard pencil probe. However, several factors must be considered when one is evaluating flow in the brachial or femoral artery for evidence o f a PDA. in the normal patient, retrograde flow exists in the femoral artery and brachiocephalic artery? -3 The degree of this retrograde flow is directly proportional to the vascular impedance beyond the monitoring site. The higher the impedance the greater will be the degree of retrograde flow present. Thus, situations which predispose to significant vasoconstriction, thus raising impedance, may increase retrograde flow in these arteries without a PDA being present. This point has been raised by Lees et al, but we feel that it must be emphasized so that a false diagnosis of a PDA is not made. We chose to evaluate flow in the descending aorta rather than a more peripheral artery, such as the femoral artery, since the vascular impedance beyond the monitoring site in the descending aorta is less variable, because there is a much larger vascular bed distal to the descending aorta than there is distal to the femoral artery. Thus, alterations in flow patterns due to changes in systemic vascular impedance are minimized. If the above considerations are kept in mind, monitoring femoral arterial flow velocity by Doppler ultrasonography can be used successfully to
853
3.
Patel D J, Greenfield JC Jr, Austen WG, Morrow AG, and Fry DL: Pressure-flow relationships in the ascending aorta and femoral artery of man, J Appl Physiol 20:459, 1965. O'Rourke MF: Pressure and flow waves in systemic arteries and the anatomical design of the arterial system, J Appl Physiol 23:139, 1967. Mills C J, G-abe IT, Gault JH, Mason DT, Ross J Jr, Braunwald E, and Shillingford JP: Pressure-flow relationships and vascular impedance in man, Cardiovas Res 4:405, 1970.
Staphylococcal protein A in diagnosis of congenital infections To the Editor: Readers of the recent article by Tuomanen and Powell' on the use of staphylococcal protein A in serologic diagnosis of congenital infections cannot independently judge the accuracy of the authors' conclusions. The criteria used for the diagnoses of congenital infections (other than for the method being evaluated) were not stated, Some diagnoses were made by serologic tests performed at the Center for Disease Control, but the reader is not told what serologic tests were performed or what the findings were. Some diagnoses were made by isolation of pathogens, but isolation of pathogens does not prove that IgM antibody is present and cannot be used as a standard by which to judge the validity of the authors' procedure for detection of IgM / antibody. The number of serum samples from congenitally infected infants was small, especially from infants infected with Toxoplasmagondii (two samples) and Treponema pallidum (one sample). c a n we extrapolate from these findings to other cases of suspected infections with these organisms? No uninfected children with maternal antibodies to T. gondii or T. pallidum were studied; we cannot know how effective adsorption with staphylococcal protein A would be in differentiating such children from congenitally infected ones. The statement is made, "accurate serologic diagnosis of congenital infection requires an initial separation of fetal IgM from transplacentally acquired maternal IgG by sucrose density centrifugation or by gel filtration." tn fact, IgM specific antibody can be detected by several methods, inc!uding immunofluorescence 2. ~ and enzyme-linked immunosorbent assay, 4,~ without prior separation of immunoglobulin classes.
Editorial correspondence
The Journal of Pediatrics May 198I
T a b l e . T h e clinical a n d l a b o r a t o r y d a t a
Patient 1 Cytochemical staining PAS Sudan Black Esterase Specific Nonspecific Immunologic marker Pre- and postblood transfusion Hemoglobin (gm/dl) White blood cell (per mm:') Blast (%) Platelet (per m m ~) Uric acid (mg/dl) Calcium (mg/dl) Phosphorus (mg/dl) Urea nitrogen (mg/dl) Creatinine (mg/dl) Quantity of blood exchanged Outcome
Patient 2
Patient 3
Negative Negative
Positive Negative
Positive Negative
Negative Negative T-cell (with anterior mediastinal mass) Pre Post
Negative Negative Non-B, N o n T-cell
Negative Negative Non-B, N o n T-cell
]
Post
11.9
2.5
8.8
5.1 1.0 million
331,000
130,000
128,000
39,300
4,400
6,500
93 38,000 11.3 9.3 3.4
45,000 7.0 8.0 4.2
85 20,000 10.5 9.5 5.5
82 166,000 8.8
0. 250,000 5.8 9.4 4.3
0. 90,000 ----
18
16
12
--
--
Partial (89 of blood volume) Relapsed in marrow 5 m o and died 8 mo after diagnosis
Not done
Negative Negative Not applicable
Pre
4.7
1. l
Negative Positive
Post
12.0
1.0
16.0 -
Partial (89 of blood volume) C C R 10 m o currently
-
Partial (~A of blood volume) C C R - 1 3 m o currently
Patient 5
Positive Negative
Pre
8.6
1.2
Patient 4
Pre
Post
Pre
Post
14.3
3.3
9.6
500*
240,000
133,000
23,000 8.5 8.7 1.8
96 13,000 4.9 9.8 3.9
50,000 3.2 8.4 4.6
86 85,000 11.4 10.3 5.4
I4
21.
18
0.8
0.8
Partial (zA of blood volume) C C R - 4 yr currently (one year off theraPY)
1.5
0.9
Partial (~A of blood volume) Failed to attain remission, died 7 m o after diagnosis
CCR = Continuous complete remission. *Following two exchange transfusions with concomitant cyclophosphamide, solucortef and vincristine.
anemia with partial exchange transfusion, A m J Dis Child 131"60 1977. Simone JV, Verzosa MD, and Rudy JA: Initial features and prognosis in 363 children with acute lymphocytic leukemia, Cancer 36"2099, 1975.
Doppler ultrasonography in evaluation of PDA shunting To the Editor: The report by Serwer and colleagues' describing the use of continuous wave Doppler ultrasonography to assess descending aorta flow reversal during diastole in premature infants with patent ductus arteriosus (PDA) is of great interest. As an alternative to descending aorta signals, we have recorded signals from the brachial (BA) and femoral (FA) arteries of 74 premature infants suspected of having a PDA. The directional flow patterns observed in RBA and FA recordings have been usefuI in detecting "silent" PDA, and approximating diastolic run-off.
A "pencil" probe and directional Doppler unit (Parks electronics Model 806-C, Beaverton, Ore.) were used. The bidirectional audiosignal was monitored stereophonically and recorded at 50 ram/second on a Beckman polygraph. With large, surgically proven PDA (n = 6) FA reverse/ forward ratio ( R / F ) averaged 0.33 preoperatively, and was always < 0.05 postoperatively; RBA R / F was 0.26 preoperatively and < 0.05 postoperatively. With moderate left-to-right P D A shunting (n = 31), where subsequent events provided compelling evidence that a PDA had been present (e.g., m u r m u r disappearance, surgical, or autopsy visualization), a typical pattern was seen: R / F 0.20 to 0.33 in FA, while R / F in RBA was < 0.05; R / F in left BA was more variable. This pattern (FA reverse flow > RBA reverse flow) appears to be specific for ductus shunting and is consistent with the cineaortographic and pressure wave dynamics described by Spach et al.'-' Provided the limbs are warm, and no catheter or thrombus obstructs the artery, false positives (for reverse flow) are not seen. False negatives can occur if the vascular resistance of the limbs is lowered with respect to other organs, e.g., following skeletal muscle paralysis. A false negative also occurred in one infant in
Volume 98 Number 5
Editorial correspondence
whom a catheter-obstructed RFA showed no flow reversal while flow reversal was seen in the unobstructed LFA. Doppler evaluation of arterial flow patterns in the presence of a PDA is a valuable noninvasive tool, and we congratulate the Duke University group on a thoughtful and important report. Martin H. Lees, M.D. James D. Newcomb, B.A. Cecille O. Sunderland, M.D. Paul Droukas, M.D. John W. Reynolds, M.D. Department of Pediatrics University of Oregon Health Sciences Center Portland, OR 97201
assess the presence or absence of PDA shunting, as Lees and coworkers have shown. Gerald A. Serwer, M.D. Brenda E. Armstrong, M.D. Page A. W. Anderson, M.D. Department of Pediatrics Division of Pediatric Cardiology Duke University Medical Center Durham, NC 27710 REFERENCES
1.
2. REFERENCES
1.
2.
Serwer GA, Armstrong BE, and Anderson PAW! N o n invasive detection of retrograde descending aortic flow in infants using continuous wave Doppler ultrasonography. J PEDIATR 97:394, 1980. Spach MS, Serwer GA, Anderson PAW, Canent RV Jr, and Levin AR: Pulsatile aortopulmonary pressure-flow dynamics of patent ductus arteriosus in patients with varying hemodynamic states, Circulation 61:110, 1980.
Reply To the Editor: The excellent work of Lees and coworkers again confirms the utility of using continuous wave Doppler ultrasonography to detect abnormal arterial flow patterns in the presence of certain disease states, in this case, the presence of a patent ductus arteriosus. Detection of flow in the femoral and brachial arteries is easily performed and, unlike our studies, does not require a flat probe but can utilize a more standard pencil probe. However, several factors must be considered when one is evaluating flow in the brachial or femoral artery for evidence o f a PDA. in the normal patient, retrograde flow exists in the femoral artery and brachiocephalic artery? -3 The degree of this retrograde flow is directly proportional to the vascular impedance beyond the monitoring site. The higher the impedance the greater will be the degree of retrograde flow present. Thus, situations which predispose to significant vasoconstriction, thus raising impedance, may increase retrograde flow in these arteries without a PDA being present. This point has been raised by Lees et al, but we feel that it must be emphasized so that a false diagnosis of a PDA is not made. We chose to evaluate flow in the descending aorta rather than a more peripheral artery, such as the femoral artery, since the vascular impedance beyond the monitoring site in the descending aorta is less variable, because there is a much larger vascular bed distal to the descending aorta than there is distal to the femoral artery. Thus, alterations in flow patterns due to changes in systemic vascular impedance are minimized. If the above considerations are kept in mind, monitoring femoral arterial flow velocity by Doppler ultrasonography can be used successfully to
853
3.
Patel D J, Greenfield JC Jr, Austen WG, Morrow AG, and Fry DL: Pressure-flow relationships in the ascending aorta and femoral artery of man, J Appl Physiol 20:459, 1965. O'Rourke MF: Pressure and flow waves in systemic arteries and the anatomical design of the arterial system, J Appl Physiol 23:139, 1967. Mills C J, G-abe IT, Gault JH, Mason DT, Ross J Jr, Braunwald E, and Shillingford JP: Pressure-flow relationships and vascular impedance in man, Cardiovas Res 4:405, 1970.
Staphylococcal protein A in diagnosis of congenital infections To the Editor: Readers of the recent article by Tuomanen and Powell' on the use of staphylococcal protein A in serologic diagnosis of congenital infections cannot independently judge the accuracy of the authors' conclusions. The criteria used for the diagnoses of congenital infections (other than for the method being evaluated) were not stated, Some diagnoses were made by serologic tests performed at the Center for Disease Control, but the reader is not told what serologic tests were performed or what the findings were. Some diagnoses were made by isolation of pathogens, but isolation of pathogens does not prove that IgM antibody is present and cannot be used as a standard by which to judge the validity of the authors' procedure for detection of IgM / antibody. The number of serum samples from congenitally infected infants was small, especially from infants infected with Toxoplasmagondii (two samples) and Treponema pallidum (one sample). c a n we extrapolate from these findings to other cases of suspected infections with these organisms? No uninfected children with maternal antibodies to T. gondii or T. pallidum were studied; we cannot know how effective adsorption with staphylococcal protein A would be in differentiating such children from congenitally infected ones. The statement is made, "accurate serologic diagnosis of congenital infection requires an initial separation of fetal IgM from transplacentally acquired maternal IgG by sucrose density centrifugation or by gel filtration." tn fact, IgM specific antibody can be detected by several methods, inc!uding immunofluorescence 2. ~ and enzyme-linked immunosorbent assay, 4,~ without prior separation of immunoglobulin classes.